Existing Substances Evaluation: Draft Screening Assessment for the Challenge 72102-55-7

Draft Screening Assessment for the Challenge

Methylium, [4-(dimethylamino)phenyl]bis[4-(ethylamino)-3-methylphenyl]-, acetate (MAPBAP acetate)

Chemical Abstracts Service Registry Number
72102-55-7

Environment Canada
Health Canada

January 2010

Synopsis

Pursuant to section 74 of the Canadian Environmental Protection Act, 1999 (CEPA 1999), the Ministers of the Environment and of Health have conducted a screening assessment on Methylium, [4-(dimethylamino)phenyl]bis[4-(ethylamino)-3-methylphenyl]- (MAPBAP acetate), Chemical Abstracts Service Registry Number 72102-55-7. This substance was identified as a high priority for screening assessment and included in the Challenge because it was found to meet the ecological categorization criteria for persistence, bioaccumulation potential and inherent toxicity to non-human organisms and is believed to be in commerce in Canada .

The substance MAPBAP acetate was not considered to be a high priority for assessment of potential risks to human health, based upon application of the simple exposure and hazard tools developed by Health Canada for categorization of substances on the Domestic Substances List. Therefore, this assessment focuses on information relevant to the evaluation of ecological risks.

MAPBAP acetate is an organic substance that is used in Canada and elsewhere as a cationic dye mainly in the production of paper products. The substance is not naturally produced in the environment. Between 10 001 and 100 000 kg of MAPBAP acetate were imported into Canada in 2006. The quantity of MAPBAP acetate imported into Canada , along with the known uses of this substance, indicate that it could be released into the Canadian environment.

Based on reported use patterns and certain assumptions, most of the substance ends up in wastewater, is disposed of in landfills, or is recycled. Based on its physical/chemical properties and partitioning behaviour, MAPBAP acetate could be found in water, sediments, or soil. It is not expected to be significantly present in air.

Based on its physical and chemical properties, MAPBAP acetate is not expected to degrade quickly in the environment. It is persistent in water, soil and sediments. MAPBAP acetate meets the criteria for persistence, but not bioaccumulation potential, as set out in the Persistence and Bioaccumulation Regulations. In addition, modelled and read-across acute aquatic toxicity values indicate that MAPBAP acetate is potentially highly hazardous to aquatic organisms.

Although no releases of MAPBAP acetate were reported in response to a survey under Section 71 of CEPA, releases to the environment could occur given the substance’s current use as a paper dye. A site-specific risk quotient analysis was performed for the aquatic medium at 11 industrial sites to determine whether there is potential for ecological harm in Canada . The site-specific analysisyielded a predicted environmental concentration (PEC) exceeding 0.001 mg/L for 10 of the 11 the sites analyzed. When these concentrations were compared to the predicted no-effect concentration (PNEC), based on experimental read-across data, the resulting risk quotients (PEC/PNEC) exceeded 1 at 10 of the 11 sites.

The potential for exposure of the general population to MAPBAP acetate from environmental media is expected to be negligible. Exposure to MAPBAP acetate from consumer products (newsprint dye) is expected to be negligible for the intended purpose of the product (negligible dermal exposure for reading activities) and low for incidental events such as mouthing exposure by toddlers.

As exposure of the general population in Canada based on the use of the substance as a paper dye is expected to be low to negligible, the risk to human health is considered to be low.

No empirical data was identified for MAPBAP acetate. The outputs of QSAR predictions for carcinogenicity and genotoxicity were mixed. Information from analogues suggests possible flags for carcinogenicity and genotoxicity and developmental toxicity.

Based on read across and modelled data for persistence, bioaccumulation and aquatic toxicity, and the characterization of risk to aquatic organisms, it is proposed that MAPBAP acetate is entering the environment in a quantity or concentration or under conditions that have or may have an immediate or long-term harmful effect on the environment or its biological diversity.

This substance will be included in the Domestic Substances List inventory update initiative. In addition, and where relevant, research and monitoring will support verification of assumptions used during the screening assessment.

Based on the information available, it is concluded that MAPBAP acetate meets one or more of the criteria set out in section 64 of the Canadian Environmental Protection Act, 1999.

Introduction

The Canadian Environmental Protection Act, 1999 (CEPA 1999) (Canada 1999) requires the Minister of the Environment and the Minister of Health to conduct screening assessments of substances that have met the categorization criteria set out in the Act to determine whether these substances present or may present a risk to the environment or human health. Based on the results of a screening assessment, the Ministers can propose to take no further action with respect to the substance, to add the substance to the Priority Substances List (PSL) for further assessment, or to recommend that the substance be added to the List of Toxic Substances in Schedule 1 of the Act and, where applicable, the implementation of virtual elimination.

Based on the information obtained through the categorization process, the Ministers identified a number of substances as high priorities for action. These include substances that

The Ministers therefore published a notice of intent in the Canada Gazette, Part I, on December 9, 2006 (Canada 2006), that challenged industry and other interested stakeholders to submit, within specified timelines, specific information that may be used to inform risk assessment, and to develop and benchmark best practices for the risk management and product stewardship of those substances identified as high priorities.

methylphenyl]-, acetate was identified as a high priority for assessment of ecological risk as it was found to be persistent, bioaccumulative and inherently toxic to aquatic organisms and is believed to be in commerce in Canada. The Challenge for this substance was published in the Canada Gazette on January 31, 2009 (Canada 2007). A substance profile was released at the same time. The substance profile presented the technical information available prior to December 2005 that formed the basis for categorization of this substance. As a result of the Challenge, submissions of information pertaining to the use of the substance were received.

methylphenyl]-, acetate was determined to be a high priority for assessment with respect to the environment, it did not meet the criteria for GPE or IPE and high hazard to human health based on classifications by other national or international agencies for carcinogenicity, genotoxicity, developmental toxicity or reproductive toxicity. Therefore, this assessment focuses principally on information relevant to the evaluation of ecological risks.

Under CEPA 1999, screening assessments focus on information critical to determining whether a substance meets the criteria for defining a chemical as toxic as set out in section 64 of the Act, where

Screening assessments examine scientific information and develop conclusions by incorporating a weight of evidence approach and precaution.

This draft screening assessment includes consideration of information on chemical properties, hazards, uses and exposure, including the additional information submitted under the Challenge. Data relevant to the screening assessment of this substance were identified in original literature, review and assessment documents, stakeholder research reports and from recent literature searches, up to September 2009 for ecological sections of the document. The draft screening assessmentdoes not represent an exhaustive or critical review of all available data. Rather, it presents the most critical studies and lines of evidence pertinent to the conclusion.

This draft screening assessment was prepared by staff in the Existing Substances Programs at Health Canada and Environment Canada and incorporates input from other programs within these departments. The ecological and human health portions of this assessment have undergone external written peer review/consultation. Additionally, the draft of this screening assessment was subject to a 60-day public comment period. Although external comments were taken into consideration, the final content and outcome of the screening risk assessment remain the responsibility of Health Canada and Environment Canada.

The critical information and considerations upon which the assessment is based are summarized below.

Substance Identity

MAPBAP acetate

For the purposes of this document, this substance will be referred to as MAPBAP acetate, derived from the DSL name. MAPBAP acetate belongs to a class of dyes known as cationic triarylmethanes. The class can be further sub-divided into those where the charge on the cation (triarylmethane moiety) is localized or delocalized. MAPBAP acetate belongs to the latter sub-category (Hunger 2003) implying that the bond holding the cationic and anionic components of the structure together is at least partly covalent.

Physical and Chemical Properties

No experimental data are available for MAPBAP acetate. At the Environment Canada-sponsored Quantitative Structure-Activity Relationship (QSAR) Workshop in 1999 (Environment Canada 2000) modelling experts identified many structural classes of pigment and dyes as being “difficult to model” using QSARs. Some physical and chemical properties of many of the structural classes of dyes and pigments are not amenable to prediction by models. Under such circumstances, a "read-across" approach is considered which employs close analogues, to determine the approximate physical and chemical properties of MAPBAP acetate. A search of the ChemID database yielded a number of suitable analogues which are described in Table 2. Experimental data for these analogues, when available, were used as extrapolated (read-across) values for MAPBAP acetate or as supporting values for the weight of evidence.

A limited number of read-across data was found for the selected analogues and, therefore, predicted values are also used for MAPBAP acetate and the uncertainties of the predictions are noted.

Table 3 below contains predicted physical-chemical properties of the neutral form of MAPBAP acetate that are relevant to its environmental fate. Analogue data are available for water solubility. The water solubility of Ethyl Violet (CAS# 2390-59-2) is 9000 mg/L (Green 1990). There is an indication that triphenylmethane acetates are more soluble than the chlorides (Pfenninger 1985) indicating the water solubility of MAPBAP acetate is high.

Table 3. Physical and chemical properties for the neutral form of MAPBAP acetate and analogues

Sources

Information gathered from the CEPA 1999 Section 71 notices for the 2005 and 2006 calendar years indicates that MAPBAP acetate was not manufactured in Canada in a quantity meeting the 100 kg reporting threshold (Canada 2006; Environment Canada 2009a). For the 2005 calendar year, fewer than four Canadian companies reported importing MAPBAP acetate (either alone, or contained in a mixture, product or manufactured item) in the 1 001 to 10 000 kg/year range.

For the 2006 calendar year, fewer than four Canadian companies reported importing MAPBAP acetate (either alone, or contained in a mixture, product or manufactured item) in the 10 001 to 100 000 kg/year range (Environment Canada 2009a). ,Fewer than twenty companies reported using MAPBAP acetate and/or were identified by importers as customers who used MAPBAP acetate, in a total quantity between 10 001–100 000 in 2006 (Environment Canada 2009a).

During the 1986 calendar year, it was reported that approximately 100 000 kg of MAPBAP acetate was manufactured, imported or in commerce in Canada (Environment Canada 1988). Fewer than four companies reported using MAPBAP acetate during the calendar years 1984 to 1986.

Products containing MAPBAP acetate may enter the country even if they are not identified as such in the section 71 survey because they may be imported unknowingly in manufactured items, or in quantities below the 100 kg reporting threshold for the survey.

Available information is currently not sufficient to derive a quantitative estimate of the importance of this source.

Uses

The use reported in the responses to the CEPA 1999 Section 71 notices for the 2005 and 2006 calendar years (Canada 2006; Environment Canada 2009a) is paper dye. Another use for MAPBAP acetate, reported in response to the section 71 survey for 2006, was indicated as Confidential Business Information (CBI).

The uses reported in the DSL nomination data were “Colourant - pigment/stain/dye/ink” and “Formulation Component” (Environment Canada 1988).

Releases to the Environment

Responses to a notice issued under section 71 of CEPA 1999 indicated no reported releases of MAPBAP acetate to the environment in the calendar year of 2006 (Environment Canada 2009a). MAPBAP acetate is not a reportable substance to the Canadian National Pollutant Release Inventory (NPRI 2008) or to the U.S. Toxics Release Inventory (TRI 2007); therefore no release data were available from these sources.

The losses of MAPBAP acetate via various routes during its lifecycle are estimated based on regulatory survey data, industry data and data published by different organizations. The losses are grouped into six types: (1) discharge to wastewater; (2) emission to air; (3) loss to land; (4) chemical transformation; (5) disposal to landfill; (6) disposal by recycling; and (7) disposal by incineration. Losses may occur at one or more of the substance's lifecycle stages that include manufacture, industrial use, consumer/commercial use, and disposal. To assist in estimating these losses, a spreadsheet (Mass Flow tool) was used that incorporates all data and assumptions required for the estimation (Environment Canada 2009). Unless specific information on the rate or potential for release of the substance from landfills, recycling operations and incinerators is available, the Mass Flow tool does not quantitatively account for releases to the environment from these waste disposal methods.

In the context of the estimation assisted by the Mass Flow tool, the discharge to wastewater refers to raw wastewater prior to any treatment, either on-site industrial wastewater treatment or off-site municipal sewage treatment. In a similar manner, the loss via chemical transformation refers to changes in substance identity that occur within the manufacture, industrial use, or consumer/commercial use stages, but excludes those during waste management operations such as incineration and wastewater treatment.

The losses estimated for MAPBAP acetate over its lifecycle are presented in Table 4 (Environment Canada 2009). Taking into account its use as a paper dye, 18.3 % of the total quantity of the substance in Canadian commerce is expected to be released to wastewater. In general, wastewater is a common source for releases to water and soil (e.g., application of biosolids) through wastewater treatment facilities.

MAPBAP acetate is also expected to be released to the environment via routes other than wastewater. MAPBAP acetate disposed of in a landfill will largely remain there because of its low vapour pressure and high logK_oc.

MAPBAP acetate is expected to be used in some manufactured items and consumer products such as dyed paper. Although no information is available on the quantity of manufactured items and consumer products containing MAPBAP acetate that are imported into Canada, it is anticipated that the proportions lost to the various routes would not be significantly different from those estimated here. However, the quantities sent for waste management would be higher if importation of these items were taken into consideration. Available information is currently not sufficient to derive a quantitative estimate for these losses.

Environmental Fate

According to its uses and the mass flow tool results presented in Table 4, MAPBAP acetate is released to water during the processing and use stages, but could partition to sediments. It may also reside in soil as the result of biosludge application.

Due to its high water solubility, based on read-across data, (see Table 3 above), MAPBAP acetate, once released to water, will tend to partition initially to that medium where it will ionize at environmental pHs. However, because the ionized MAPBAP acetate molecule will yield a reactive carbocation (MAPBAP), most MAPBAP acetate released to water will probably react with available anionic material, including humic acid that is present in the water. The US EPA makes the following recommendation for the testing of new cationic dyes: “…two fish acute toxicity tests are recommended with known amounts of humic acid added to the dilution water. This testing is necessary to measure the mitigating effects of dissolved organic carbon (DOC) on the toxicity of the cationic dye.” ( US EPA 2002).

MAPBAP acetate may enter soil with sludge from wastewater treatment plants, which may be used for soil enrichment, or through disposal of sludges and coloured papers in landfills. Volatilization from dry or moist soil surfaces is an unimportant fate process because MAPBAP acetate has low vapour pressure (see Table 2). If released to soil, MAPBAP acetate will remain there, based on its high predicted logKoc value.

MAPBAP acetate is a solid at room temperature and based on its vapour pressure and Henry’s Law constant, it is not released to air.

Persistence and Bioaccumulation Potential

Environmental Persistence

No experimental biological degradation data for MAPBAP acetate have been identified. There are no suitable analogues with experimental data for degradation so a QSAR-based weight-of-evidence approach (Environment Canada 2007) was applied using the degradation models shown in Table 5 below. The models for persistence use chemical structure as the basis for their predictions. Structural fragments of MAPBAP acetate are covered in the models and predictions are consistent with what would be expected for this type of compound, i.e., a branched aromatic. Chemical speciation (ionic vs. neutral form) is less relevant for biodegradation predictions than for bioaccumulation and toxicity predictions.

The BIOWIN models were used to estimate the substance’s persistence in water, and these predictions were extrapolated to soil and sediment, where MAPBAP is expected to partition to some degree.

The structural components of the MAPBAP acetate carbocation are represented in the model fragment sets and predictions are consistent with what would be expected for the biodegradation potential of this tri-phenyl structure. However, there is some uncertainty as chemicals of overall structural similarity to MAPBAP acetate are not contained in their training sets.

In air, a predicted atmospheric oxidation half-life value of 0.02 days (see Table 5 above) indicates that MAPBAP acetate will be rapidly oxidized. The substance is not expected to react with other photo-oxidative species in the atmosphere, such as O₃nor is it likely to degrade via direct photolysis. Therefore, it is expected that reactions with hydroxyl radicals will be the most important fate process in the atmosphere for MAPBAP acetate. With a half-life of 0.02 days via reactions with hydroxyl radicals, MAPBAP acetate is considered not persistent in air.

In water, a predicted hydrolysis half-life value of 1059 days at pH 7 (see Table 5 above) demonstrates that this chemical will be slowly hydrolysed. Other fate processes in water such as biodegradation, need to be considered to determine the overall level of persistence in this medium.

Results for the three BIOWIN ultimate biodegradation models (BIOWIN Sub-models 3, 5 and 6) indicate that biodegradation is slow and that the half-life in water would be > 182 days. Although the result from BIOWIN Sub-model 4 indicates that primary biodegradation may be faster and that the half-life from primary transformation in water would be <182 days, the identity of the degradation products is not known. In addition, the ultimate degradation predictions from CPOPs and the OECD Toolbox indicate a very slow rate of biodegradation.

According to the Ecological and Toxicological Association of Dyes and Organic Pigments Manufacturers, with some exceptions, dyes are considered essentially non-biodegradable under aerobic conditions (ETAD 1995). Repeated evaluation of ready and inherent biodegradability using accepted screening tests (see the OECD Guidelines for the Testing of Chemicals website) have confirmed this assumption (Pagga and Brown 1986; ETAD 1992). Based on the chemical structure of MAPBAP acetate, there is no reason to suspect that biodegradation will be other than that described for dyes generally (ETAD 1995).

Considering all model results and the structure of the MAPBAP acetate molecule (triphenylmethane), the biodegradation half-life of MAPBAP acetate is > 182 days in water.

Using an extrapolation ratio of 1:1:4 for a water: soil: sediment biodegradation half-life (Boethling et al 1995), the half-life in soil is also >182 days and the half-life in sediments is >365 days. This indicates that MAPBAP Acetate is expected to be persistent in soil and sediments.

Based on the information presented above, MAPBAP acetate meets the persistence criteria in water, soil, and sediment (half-lives in soil and water ≥ 182 days and half-life in sediment ≥ 365 days), but does not meet the criteria for air (half-life in air ³ 2 days) as set out in the Persistence and Bioaccumulation Regulations (Canada 2000).

Potential for Bioaccumulation

There are no empirical bioaccumulation data available for MAPBAP acetate. There are, however, empirical bioaccumulation data for Malachite Green (CAS RN 569-64-2), an analogue of MAPBAP acetate. This data is presented below in Table 6a.

Table 6a. Empirical data for bioaccumulation of Malachite Green (analogue of MAPBAP acetate)

Since no experimental bioaccumulation factor (BAF) data and only one experimental bioconcentration factor (BCF) result were found for analogues of MAPBAP acetate, a predictive approach was applied using available BAF and BCF models as shown in Table 6b below. According to the Persistence and Bioaccumulation Regulations (Canada 2000) a substance is bioaccumulative if its BCF or BAF is > 5000, however measures of BAF are the preferred metric for assessing bioaccumulation potential of substances. This is because BCF may not adequately account for the bioaccumulation potential of substances via the diet, which predominates for substances with log K_ow > ~4.0 (Arnot and Gobas 2003). Kinetic mass-balance modelling is in principle considered to provide the most reliable prediction method for determining the bioaccumulation potential because it allows for metabolism correction as long as the log K_ow of the substance is within the log K_ow domain of the model.

The mass-balance bioaccumulation model BCFBAFWIN was run for MAPBAP acetate. Read-across data for the logKow (0.51) was used for model input. MAPBAP acetate is at least partly ionic, has high water solubility (based on read-across data) and is probably completely dissociated at environmental pHs. The BAF modelling considers a food web that includes benthic invertebrates (Arnot and Gobas 2003). The predicted BAF is 1.015 L/kg.(see Table 6b below).

Table 6b. Fish BAF and BCF predictions for MAPBAP acetate using the Arnot-Gobas kinetic model (2003) and considering metabolism.

Table 6c. Additional Modelled data for bioaccumulation that considers metabolism

Ionic dyes (including acid and direct dyes) are generally considered to have a very low bioaccumulation potential based on results of studies with various dyes (ETAD 1995).

Considering the available evidence, MAPBAP acetate does not meet the bioaccumulation criteria (BCF, BAF ≥ 5000) as set out in the Persistence and Bioaccumulation Regulations (Canada 2000).

Potential to Cause Ecological Harm.

Ecological Effects Assessment

There are no empirical ecotoxicity data available for MAPBAP acetate and therefore data from chemical analogues is used. Based on the available experimental evidence (Table 7a), MAPBAP acetate is expected to cause harm to aquatic organisms at relatively low concentrations (i.e., acute LC₅₀s are < 1 mg/L).

Table 7a. Empirical data for aquatic toxicity of analogues of MAPBAP acetate

An empirical acute toxicity study for a close analogue of MAPBAP acetate (Basic Violet 3, CAS RN 548-62-9) for Ozirias latipes (Table 7a) found a 48-hour LC₅₀ of 0.1 mg/L, indicating that MAPBAP acetate is hazardous to aquatic organisms at relatively low concentrations (i.e., LC/EC₅₀s ≤ 1 mg/L). This conclusion is supported by empirical acute toxicity studies for other structural analogues of MAPBAP acetate.

Given that there are no empirical ecotoxicity data available for MAPBAP acetate, the aquatic toxicity was also assessed using QSAR models.

Table 8. Modelled data for aquatic toxicity of neutral form of MAPBAP acetate

The US EPA has developed a list called the “TSCA New Chemicals Program (NCP) Chemical Categories.” One of the categories is cationic dyes. MAPBAP acetate is a cationic dye. The EPA indicates that cationic dyes are water soluble substances that are toxic to fish, daphnids, and algae (EPA 2000). It should be noted, however, that the EPA’s ecotoxicity concerns about cationic dyes are based on QSAR predictions for delocalized cationic dyes.

The modelled evidence supports the analogue data used to show that MAPBAP acetate is potentially highly hazardous to aquatic organisms (acute LC/EC₅₀≤ 1.0 mg/L).

Since MAPBAP acetate could partition to sediment and may potentially enter soil from biosludge which is commonly used for soil enrichment, as well as from the disposal of products that degrade and release these solvent dyes, it would be desirable to have toxicity data for sediment and soil organisms. However, no suitable ecological effects studies were found in media other than water. The toxicity potential is also likely to be low in sediment- and soil-dwelling species, however, considering the lack of bioaccumulation potential and bioavailability as well as its physical and chemical properties, although this cannot be substantiated due to lack of suitable whole organism toxicity data

Ecological Exposure Assessment

No data concerning concentrations of this substance in water in Canada have been identified.

Industrial Release

A site-specific exposure analysis was conducted for the aquatic compartment at a total of 11 sites where MAPBAP acetate was used as a dye in the production of paper products. The quantity of the substance used at each site was in the range of 1000 to 10 000 kg/year (Environment Canada 2009a). Dye is used with a fixative to increase fixation rate to fibre; the fixation rate was assumed to be 80% (OECD 2006). The fraction lost to wastewater from the production processes was estimated at 20%. Additional loss was also expected from the cleaning of chemical containers at 0.3% for totes and 3% for drums (OECD 2009b). The wastewater containing MAPBAP acetate was then treated by either on-site or off-site secondary wastewater treatment systems with a model predicted removal rate of 3.4% (ASTreat 1.0). The effluents from these treatment systems were then released to rivers, lakes or costal waters and a dilution factor up to 10 was used in deriving the predicted environmental concentrations (PECs) from the effluent concentrations. The estimated PECs for the 11 industrial sites ranged from of 0.001 mg/L to 0.03 mg/L (Environment Canada 2009c). These PEC values represent the level of exposure in the receiving water near the point of the discharge from the wastewater treatment plant at each site.

The approach taken in this ecological screening assessment was to examine various supporting information and develop conclusions based on a weight-of-evidence approach and using precaution as required under CEPA 1999. Lines of evidence considered include results from a conservative risk quotient calculation, as well as information on persistence, bioaccumulation, inherent toxicity, sources and fate of the substance.

MAPBAP acetate is expected to be persistent in water, soil and sediment, but not in air. It is also expected to have a low bioaccumulation potential. The importation volumes of MAPBAP acetate into Canada , along with information on its uses, indicate potential for some releases into the Canadian environment. Once released into the environment, it could be found in water, soil, or sediment depending on the medium of release. Based on analogue data, MAPBAP acetate is expected to have high potential for toxicity to aquatic organisms.

A site-specific risk quotient analysis was performed for the aquatic medium at 11 industrial sites to determine whether there is potential for ecological harm in Canada .

The estimated PECs for the 11 industrial sites ranged from 0.001 mg/L to 0.03 mg/L (Environment Canada 2009c).

A predicted no-effect concentration (PNEC), based on experimental read-across data, was derived from the acute toxicity value of 0.1 mg/L for the medaka fish, by dividing this value by an assessment factor of 100 (10 to account for interspecies and intraspecies variability in sensitivity and 10 to estimate a long-term no-effects concentration from a short-term LC_50,) to give a value of 0.001 mg/L. The resulting risk quotients (PEC/PNEC).ranged from 0.9 to 32.8 and exceeded 1 at 10 of the 11 industrial sites.

This information indicates that MAPBAP acetate could be causing ecological harm in Canada .

As noted previously, when MAPBAP acetate is released into a water body, it partitions into suspended particulate matter and to bottom sediments, where sediment-dwelling organisms would be exposed to the substance. No environmental monitoring data or toxicity data specific to sediment-dwelling organisms were found, so a risk quotient based on exposure in sediment pore water may be calculated based on the aquatic compartment PEC and PNEC values presented above and used for sediment risk characterization. In the calculation, bottom sediment and its pore water are assumed to be in equilibrium with the overlying water and benthic and pelagic organisms are assumed to have similar sensitivities to the substance. Therefore the PEC and PNEC for sediment pore water is considered to be the same as for the aquatic compartment. This equilibrium approach would therefore result in risk quotients for the sediment compartment that are the same as for the aquatic compartment.

Uncertainties in Evaluation of Ecological Risk

There are no experimental data for MAPBAP acetate. There are no suitable read-across (analogue) data for persistence. This necessitated the use of model predictions for persistence. The model predictions are for the neutral form of the molecule, but it is not entirely certain what form this substance will assume at environmental pHs (dissociated or non-dissociated) although it is likely dissociated. In addition, there is uncertainty with the model predictions for physical-chemical properties, persistence and bioaccumulation potential because there are no triarylmethane dyes in the training sets for these models.

Read-across data was used for some physical-chemical properties (water solubility, logKow), bioaccumulation potential and aquatic toxicity.

Uncertainty exists because of the lack of information on environmental concentrations (e.g., monitoring data) of MAPBAP acetate in Canada , or elsewhere.

There is uncertainty associated with the fraction of MAPBAP acetate in commerce that is released, and with the fraction that is removed in sewage treatment plants.

Although no information is available on the quantity of MAPBAP acetate that is imported in consumer products, it is anticipated that given the diffuse nature of the releases the concentrations of MAPBAP acetate in the various environmental media would not be significantly different. It is also recognised that potential releases from waste disposal sites could be possible and contribute to overall environmental concentration. However available information is currently not sufficient to derive a quantitative estimate for these releases.

Potential to Cause Harm to Human Health

Exposure Assessment

There were no data identified for MAPBAP acetate in environmental media, regardless of location. In the absence of release data from publicly available inventories and since in responses to a notice issued under section 71 of CEPA 1999, no releases were reported, as a conservative approach, environmental concentrations were estimated using the loss percentages predicted by the Mass Flow tool by Environment Canada (see Table 4) (Environment Canada 2009c). The percentages were applied to the total quantity of MAPBAP acetate in Canadian commerce in 2006.

The total quantity in commerce was conservatively assumed to be up to 100 000 kg (Environment Canada 2009a). The loss quantities are estimated as: 18 300 kg to water through wastewater and 39 500 kg to soil through leaching from landfill. While 18.3% of the total quantity in Canadian commerce is assumed to represent loss through wastewater, this loss is likely an overestimate of release as treatment of the wastewater at municipal sewage treatment plants is not considered.

The estimated losses were used in ChemCAN, a Canada-specific environmental exposure model, to estimate concentrations in various environmental media (ChemCAN 2003). This model differs from the point source models used in the ecological assessment section of the document, which provide estimates of exposure near release points, in that it is a regional far-field level III fugacity model that is used to estimate average concentrations in various media to inform human exposure estimates. The predicted environmental concentrations are presented in Appendix 1 and were used as surrogates for measured data in deriving intake estimates. The estimated concentration in ambient air was used as a surrogate for indoor air data. In addition, the estimated concentration in surface water was used as a surrogate for drinking water data. The intake estimates for each medium, in addition to total intake for each age group, are presented in Appendix 2. Soil is the estimated predominant source of environmental exposure, producing a maximum total daily intake of 0.01 µg/kg-bw per day for children aged 0.5 to 4 years.

MAPBAP acetate is used as a basic dye for paper. These basic dyes are intended to produce bright and deep shades with superior fastness to light exposure and washing. During the dyeing process, basic dyes exhibit high fixation to all substrates, with an average fixation of 99% in mildly acidic salt baths (ETAD 1995). In responses to a notice issued under section 71 of CEPA 1999, MAPBAP acetate was used in Canada in 2006 to dye newsprint at a concentration range of 0.06 to 0.12% by weight in the paper (Environment Canada 2009a). Unlike inks, dyes are contained within the matrix of the paper and would be anticipated to exhibit negligible migration in a dermal scenario. In addition, the preferential sorption of the cationic dye to the negatively-charged lignin of the pulp would result in minimal release of the dye upon exposure to sweat. However, toddlers of age 0.5 to 4 years are known to ingest paper during mouthing behaviours, leading to potential oral exposure. Despite the high fixation rate in mildly acidic salt baths, the highly acidic environment of the stomach (pH ≈ 2) may affect the dye fastness in an unknown manner; therefore release and availability of the dye for absorption in the gastrointestinal tract was conservatively assumed to be 100% when modelling potential exposure from this route. A paper ingestion scenario produced an estimated oral acute intake of 0.067 mg/kg-bw per event and is presented in Appendix 3.

In the United States , MAPBAP acetate is permitted as an inert ingredient in pest control products for non-food uses by the U.S. EPA (U.S. EPA 2009). However, MAPBAP acetate is not currently registered as a formulant or active ingredient in pest control products in Canada therefore this application is not considered a source of exposure for Canadians (2009 email from the Pest Management Regulatory Agency, Health Canada to Risk Assessment Bureau, Health Canada; unreferenced).

Health Effects Assessment

No empirical data was identified for MAPBAP acetate. Sources of health hazard information considered included examination of available international reviews, assessments or classifications, reviewing the available empirical data where available and the use of predictive models as appropriate. The outputs of predictive models were also considered using five different QSAR models, Topkat, Casetox Toxtree, Derek and Model Applier.

Using the representative molecular structure of MAPBAP (with the acetic acid fragment (acetate) attached to the carbon atom (attached to three aromatic rings)) we obtained the following results. Positive predictions have been obtained on five different genotoxicity endpoints and only one of these (i.e. micronucleus) is corroborated by more than one model (CASETOX and Toxtree). The Benigni-Bossa model within the Toxtree also predicts it to be a Salmonella typhimurium TA100 mutagen with metabolic activation. On the other hand, the female rat cancer models of both CASETOX and Model Applier predicted positive. The male rat cancer model of Model Applier as well as both mice models (male and female) of CASETOX predicted positive. The presence of a structural alert indicative of genotoxic carcinogenicity is another piece of supporting information that has been obtained from the Benigni-Bossa model within Toxtree. Applying the OncoLogic model to a nearly similar structure containing hydyoxyl group in place of the acetate group results in a positive carcinogenicity prediction. This prediction is based on presence of Nitrogen substituted groups on the aromatic rings.

It is important to note that the Toxtree micronucleus model is a coarse grain filter for preliminary screening of potential in vivo mutagens and the OncoLogic does not use the identical structure for prediction purposes. Also, the Ames models of CASETOX and Model Applier predict negative results whereas TOPKAT and DEREK fail to provide any information. However, in case of cancer models we have at least three models (CASETOX, Model Applier and Toxtree) that classify this chemical as a potential carcinogen. The CASETOX, Model Applier and the Toxtree are based on unique methodologies for making predictions and since they point towards a similar outcome it carries more weight.

Thus the outputs predictions were mixed for carcinogenicity (6 positives and 4 negatives), genotoxicity (6 positives and 7 Negatives), developmental (2 Positive; 18 Neg and 10 NR) and reproductive toxicity (1 Positive 12 NR).

Potential structural analogues of MAPBAP acetate for the purposes of read-across for human health toxicity information were identified using Leadscope (Leadscope 2008) and ChemID along with professional judgement. As the main structure would distribute the positive charge across the molecule through resonance structures, the acetate counter ion would likely interchange with other ions or substrates when the dye is used. Therefore, the moiety of interest from a human health toxicological perspective would be the parent molecule itself. Other similar triarylamine substances, that have empirical data, include gentian violet (CAS 548-62-9), malachite green (CAS 569-64-2), C.I. Basic Violet 4 (CAS 2390-59-2) and leucomalachite green (CAS 129-73-7) as shown in Appendix 5.

Gentian violet has been classified by the European Union as Carcinogenicity Category 2 (ECB 2002) based on carcinogenicity in experimental animals. Malachite green has been classified by the European Union as Reproductive Category 3(ECB 2003) based on developmental toxicity in experimental animals; also the NTP (2005) reported equivocal evidence of carcinogenicity in female rats and negative results for genotoxicity from an in vivo micronucleus assay and an in vitro assay in S.typhimurium (NTP 1997; 1994).

C.I Basic Violet 4 had negative in vitro genotoxicity data for mutations in a micronucleus assay and for chromosomal aberrations in Chinese Hamster Ovary cells (NICNAS 1999) and was also found to be predominately negative in vitro in assays conducted in S. typhimurium and mouse lymphoma cells (CCRIS 2009). Leucomalachite green was found to have some evidence of carcinogenicity in female mice and had positive in vivo genotoxicity data (NTP 1996, 2005).

The information obtained from the QSAR models as well as potential analogues, suggest that there may be potential carcinogenic or developmental toxicity hazards associated with the substance.

The confidence in the toxicity database is considered to be low due to the lack of available data for MAPBAP acetate

Characterization of Risk to Human Health

As exposure of the general population in Canada based on the use of the substance as a paper dye is expected to be low to negligible, the risk to human health is considered to be low.

No empirical data was identified for MAPBAP acetate. The outputs of QSAR predictions for carcinogenicity and genotoxicity were mixed. Information from analogues also suggests possible flags for carcinogenicity, genotoxicity and developmental toxicity.

Uncertainties in Evaluation of Risk to Human Health

Confidence in the environmental exposure estimates is moderate. Literature data was not identified for concentrations in environmental media however, in light of no releases reported in response to a notice issued under section 71 of CEPA 1999, in conjunction with the conservative use of loss quantities predicted by the Mass Flow Tool to represent worst-case release estimates, it is unlikely that the intake values are underestimates. Confidence in the consumer product exposure estimate is moderate. While end products in current use in Canada are considered to have been comprehensively captured in the responses to a notice issued under section 71 of CEPA 1999, the quantity of paper ingested by a toddler per mouthing event was a conservative estimate.

Due to the lack of data available for MAPBAP acetate confidence in the toxicological database is very low.

Conclusion

Based on the information presented in this draft screening assessment, it is proposed that MAPBAP acetate is entering or may be entering the environment in a quantity or concentration or under conditions that have or may have an immediate or long-term harmful effect on the environment or its biological diversity.

Based upon consideration of the available data, it is proposed that MAPBAP acetate is not a substance entering the environment in a quantity or concentration or under conditions that constitute or may constitute a danger in Canada to human life or health.

It is therefore proposed that MAPBAP acetate meets the definition of toxic as set out in section 64 of CEPA 1999. Additionally, MAPBAP acetate meets the criteria for persistence as set out in the Persistence and Bioaccumulation Regulations (Canada 2000).

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Appendix 1: Estimated concentrations of MAPBAP acetate in environmental media using ChemCAN version 6.00 (ChemCAN 2003). ^{1, 2}

Appendix 2. Estimates of total and media-specific daily intakes of MAPBAP acetate for various age groups.

Appendix 3: Exposure estimate for ingestion of multi-use paper by a toddler of age 0.5 to 4 years.

Appendix 4: Summary of (Q)SAR Results

MA – model applier;
CT – Multicase Casetox;
TK – Topkat;
TT – Toxtree;
BB – Benigni-Bossa rule;
ND – not in domain;
'-' no model available in QSAR suite
NR – no result

Appendix 5: Analogues of MAPBAP acetate considered in Human Health portion of assessment

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